Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/24024 |
Resumo: | Mycotoxins are secondary metabolites produced by fungi and represent a worldwide concern due to their global distribution and the harmful effects caused by their ingestion. This problem presents itself in its most dramatic form in farm animals, especially pigs, which are considered the farm animals most sensitive to the effects of mycotoxins. Thus, mycotoxins have been shown to be a serious economic problem, it is essential to elucidate their toxicological mechanisms and seek alternatives that minimize the damage caused by them. In this sense, phenolic compounds and other antioxidants have been shown to have the ability to protect and even neutralize the damage caused by various toxic substances, including mycotoxins. Curcumin and silymarin are two polyphenols known for their strong antioxidant activity extracted from the plants Curcuma longa and Silybum marianum, respectively. In this context, this study aimed to: a) evaluate the toxicity of ochratoxin A (OTA) in pig peripheral blood mononuclear cells and porcine kidney cells of the PK-15 cell line through the evaluation of cell viability, oxidative stress and mitochondrial activity ; b) to evaluate the protective effect of curcumin and silymarin pretreatment on PK-15 cells in vitro on the toxicity induced by OTA, fumonisin B1 (FB1) and deoxynivalenol (DON), via cellular viability assessment, oxidative stress and apoptosis; and c) to investigate the effect of pretreatment with curcumin and silymarin in the prevention of acute toxicity caused by FB1 and OTA on hepatic and kidney oxidative stress, as well as on serological biomarkers of hepatic and kidney function in mice in vivo. We observed that the toxic effects of OTA in PK-15 cells and porcine PBMCs are quite similar, exposure to OTA causes loss of cell viability, increases oxidative stress and causes inhibition of the enzymes superoxide dismutase and catalase, in addition to causing mitochondrial dysfunction , inhibiting complex I of the electron transport chain. Pretreatment with curcumin and silymarin proved to be efficient in protecting PK-15 cells from damage caused by mycotoxins; curcumin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species triggered by FB1 and DON and decreased apoptosis in cells exposed to DON. The pretreatment of cells with silymarin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species produced by FB1 and DON and decreased apoptosis in cells exposed to FB1 and DON. In the evaluation of the protective effects of curcumin and silymarin on liver and kidney toxicity caused by OTA and FB1 in mice, it was observed that both compounds, administered alone or in combination, were able to mitigate the harmful effects caused by mycotoxins, promoting improvement in liver and kidney function and preventing oxidative stress, in addition to preventing kidney tubular damage and hepatocyte necrosis caused by exposure to the mycotoxins OTA and FB1. In general, the results of this study demonstrated that both curcumin and silymarin provided protection against the harmful effects caused by exposure to mycotoxins. |
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2022-04-04T18:15:11Z2022-04-04T18:15:11Z2020-10-08http://repositorio.ufsm.br/handle/1/24024Mycotoxins are secondary metabolites produced by fungi and represent a worldwide concern due to their global distribution and the harmful effects caused by their ingestion. This problem presents itself in its most dramatic form in farm animals, especially pigs, which are considered the farm animals most sensitive to the effects of mycotoxins. Thus, mycotoxins have been shown to be a serious economic problem, it is essential to elucidate their toxicological mechanisms and seek alternatives that minimize the damage caused by them. In this sense, phenolic compounds and other antioxidants have been shown to have the ability to protect and even neutralize the damage caused by various toxic substances, including mycotoxins. Curcumin and silymarin are two polyphenols known for their strong antioxidant activity extracted from the plants Curcuma longa and Silybum marianum, respectively. In this context, this study aimed to: a) evaluate the toxicity of ochratoxin A (OTA) in pig peripheral blood mononuclear cells and porcine kidney cells of the PK-15 cell line through the evaluation of cell viability, oxidative stress and mitochondrial activity ; b) to evaluate the protective effect of curcumin and silymarin pretreatment on PK-15 cells in vitro on the toxicity induced by OTA, fumonisin B1 (FB1) and deoxynivalenol (DON), via cellular viability assessment, oxidative stress and apoptosis; and c) to investigate the effect of pretreatment with curcumin and silymarin in the prevention of acute toxicity caused by FB1 and OTA on hepatic and kidney oxidative stress, as well as on serological biomarkers of hepatic and kidney function in mice in vivo. We observed that the toxic effects of OTA in PK-15 cells and porcine PBMCs are quite similar, exposure to OTA causes loss of cell viability, increases oxidative stress and causes inhibition of the enzymes superoxide dismutase and catalase, in addition to causing mitochondrial dysfunction , inhibiting complex I of the electron transport chain. Pretreatment with curcumin and silymarin proved to be efficient in protecting PK-15 cells from damage caused by mycotoxins; curcumin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species triggered by FB1 and DON and decreased apoptosis in cells exposed to DON. The pretreatment of cells with silymarin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species produced by FB1 and DON and decreased apoptosis in cells exposed to FB1 and DON. In the evaluation of the protective effects of curcumin and silymarin on liver and kidney toxicity caused by OTA and FB1 in mice, it was observed that both compounds, administered alone or in combination, were able to mitigate the harmful effects caused by mycotoxins, promoting improvement in liver and kidney function and preventing oxidative stress, in addition to preventing kidney tubular damage and hepatocyte necrosis caused by exposure to the mycotoxins OTA and FB1. In general, the results of this study demonstrated that both curcumin and silymarin provided protection against the harmful effects caused by exposure to mycotoxins.As micotoxinas são metabólitos secundários produzidos por fungos e representam uma preocupação mundial devido à sua distribuição global e aos efeitos prejudiciais causados pela sua ingestão. Esse problema se apresenta em sua forma mais dramática nos animais de produção, especialmente os suínos, que são considerados os animais de produção mais sensíveis aos efeitos das micotoxinas. Dessa forma, as micotoxinas têm se mostrado um grave problema econômico, sendo fundamental elucidar seus mecanismos toxicológicos e buscar alternativas que minimizem os danos por elas causados. Nesse sentido, têm-se demonstrado que compostos fenólicos e outros antioxidantes têm a capacidade de proteger e até mesmo neutralizar os danos causados por várias substâncias tóxicas, incluindo as micotoxinas. A curcumina e a silimarina são dois polifenóis conhecidos por sua forte atividade antioxidante extraídos das plantas Curcuma longa e Silybum marianum, respectivamente. Neste contexto, este estudo teve por objetivos: a) avaliar a toxicidade da ocratoxina A (OTA) em células mononucleares do sangue periférico de suínos e células de rim suíno da linhagem PK-15 através da avaliação da viabilidade celular, estresse oxidativo e atividade mitocondrial; b) avaliar o efeito protetor do pré-tratamento de curcumina e silimarina sobre células renais da linhagem PK-15 de suínos in vitro sobre a toxicidade induzida por OTA, fumonisina B1 (FB1) e deoxinivalenol (DON), por meio da avaliação de viabilidade celular, estresse oxidativo e apoptose; e c) investigar o efeito do pré-tratamento com curcumina e silimarina na prevenção da toxicidade aguda causada por FB1 e OTA sobre o estresse oxidativo hepático e renal, bem como sobre biomarcadores sorológicos de função hepática e renal em camundongos in vivo. Foi observado que os efeitos tóxicos da OTA em células PK-15 e PBMCs suínas são bastante semelhantes, onde a exposição à OTA causa perda de viabilidade celular, aumenta o estresse oxidativo e causa inibição das enzimas superóxido dismutase e catalase, além de causar disfunção mitocondrial, inibindo o complexo I da cadeia transportadora de elétrons. O pré-tratamento com curcumina e silimarina se mostrou eficiente em proteger as células PK-15 de danos causados pelas micotoxinas; curcumina diminuiu a perda de viabilidade celular induzida por OTA, FB1 e DON; inibiu a formação de espécies reativas de oxigênio desencadeadas por FB1 e DON e diminuiu a apoptose em células expostas a DON. Já o pré-tratamento das células com silimarina diminuiu a perda de viabilidade celular induzida por OTA, FB1 e DON; inibiu a formação de espécies reativas de oxigênio desencadeadas por FB1 e DON e diminuiu a apoptose em células expostas a FB1 e DON. Na avaliação do efeito protetor de curcumina e silimarina sobre a toxicidade hepática e renal causada por OTA e FB1 em camundongos, foi observado que ambos os compostos, tanto quando administrados isolados, como em combinação, foram capazes de mitigar os efeitos deletérios causados pelas micotoxinas, promovendo melhora na função hepática e renal e prevenindo o estresse oxidativo, além de evitarem dano tubular renal e necrose de hepatócitos causada pela exposição às micotoxinas OTA e FB1. De maneira geral, os resultados deste estudo demonstraram que tanto a curcumina como a silimarina proporcionaram proteção contra os efeitos deletérios causados pela exposição à micotoxinas.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessToxicidadeOcratoxina AFumonisina B1DeoxinivalenolCurcuminaSilimarinaToxicityOchratoxin AFumonisin B1DeoxynivalenolCurcuminSilymarinCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAAvaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivoEvaluation of the effects of curcumin and silymarin on the toxicity induced by mycotoxins in vitro and in vivoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSanturio, Janio Moraishttp://lattes.cnpq.br/6316012260769979Loreto, Érico Silva deLeal, Daniela Bitencourt RosaDenardi, Laura BedinBauermann, Liliane de Freitashttp://lattes.cnpq.br/6747982502578613Ledur, Pauline Christ20100000000060060060060060060060006a1b29c-fde0-4a69-8097-2a9d6a9d9649d98f1f7c-c81c-43dd-91f1-cb47808c004bbee3850b-1736-40d6-af3c-3ab7d978f802c557ce44-0763-4865-8372-1163d96ba82b515d7605-6a82-4879-a6b7-7556917015052692a8bc-fe74-4278-b83e-83c3d8a4024dreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGFARMACOLOGIA_2020_LEDUR_PAULINE.pdfTES_PPGFARMACOLOGIA_2020_LEDUR_PAULINE.pdfTese de Doutoradoapplication/pdf3216607http://repositorio.ufsm.br/bitstream/1/24024/1/TES_PPGFARMACOLOGIA_2020_LEDUR_PAULINE.pdf8ccf75fa835994967b31eaec5d3b557cMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the effects of curcumin and silymarin on the toxicity induced by mycotoxins in vitro and in vivo |
title |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
spellingShingle |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo Ledur, Pauline Christ Toxicidade Ocratoxina A Fumonisina B1 Deoxinivalenol Curcumina Silimarina Toxicity Ochratoxin A Fumonisin B1 Deoxynivalenol Curcumin Silymarin CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
title_full |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
title_fullStr |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
title_full_unstemmed |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
title_sort |
Avaliação dos efeitos de curcumina e silimarina sobre a toxicidade induzida por micotoxinas in vitro e in vivo |
author |
Ledur, Pauline Christ |
author_facet |
Ledur, Pauline Christ |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Santurio, Janio Morais |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6316012260769979 |
dc.contributor.referee1.fl_str_mv |
Loreto, Érico Silva de |
dc.contributor.referee2.fl_str_mv |
Leal, Daniela Bitencourt Rosa |
dc.contributor.referee3.fl_str_mv |
Denardi, Laura Bedin |
dc.contributor.referee4.fl_str_mv |
Bauermann, Liliane de Freitas |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6747982502578613 |
dc.contributor.author.fl_str_mv |
Ledur, Pauline Christ |
contributor_str_mv |
Santurio, Janio Morais Loreto, Érico Silva de Leal, Daniela Bitencourt Rosa Denardi, Laura Bedin Bauermann, Liliane de Freitas |
dc.subject.por.fl_str_mv |
Toxicidade Ocratoxina A Fumonisina B1 Deoxinivalenol Curcumina Silimarina |
topic |
Toxicidade Ocratoxina A Fumonisina B1 Deoxinivalenol Curcumina Silimarina Toxicity Ochratoxin A Fumonisin B1 Deoxynivalenol Curcumin Silymarin CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Toxicity Ochratoxin A Fumonisin B1 Deoxynivalenol Curcumin Silymarin |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Mycotoxins are secondary metabolites produced by fungi and represent a worldwide concern due to their global distribution and the harmful effects caused by their ingestion. This problem presents itself in its most dramatic form in farm animals, especially pigs, which are considered the farm animals most sensitive to the effects of mycotoxins. Thus, mycotoxins have been shown to be a serious economic problem, it is essential to elucidate their toxicological mechanisms and seek alternatives that minimize the damage caused by them. In this sense, phenolic compounds and other antioxidants have been shown to have the ability to protect and even neutralize the damage caused by various toxic substances, including mycotoxins. Curcumin and silymarin are two polyphenols known for their strong antioxidant activity extracted from the plants Curcuma longa and Silybum marianum, respectively. In this context, this study aimed to: a) evaluate the toxicity of ochratoxin A (OTA) in pig peripheral blood mononuclear cells and porcine kidney cells of the PK-15 cell line through the evaluation of cell viability, oxidative stress and mitochondrial activity ; b) to evaluate the protective effect of curcumin and silymarin pretreatment on PK-15 cells in vitro on the toxicity induced by OTA, fumonisin B1 (FB1) and deoxynivalenol (DON), via cellular viability assessment, oxidative stress and apoptosis; and c) to investigate the effect of pretreatment with curcumin and silymarin in the prevention of acute toxicity caused by FB1 and OTA on hepatic and kidney oxidative stress, as well as on serological biomarkers of hepatic and kidney function in mice in vivo. We observed that the toxic effects of OTA in PK-15 cells and porcine PBMCs are quite similar, exposure to OTA causes loss of cell viability, increases oxidative stress and causes inhibition of the enzymes superoxide dismutase and catalase, in addition to causing mitochondrial dysfunction , inhibiting complex I of the electron transport chain. Pretreatment with curcumin and silymarin proved to be efficient in protecting PK-15 cells from damage caused by mycotoxins; curcumin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species triggered by FB1 and DON and decreased apoptosis in cells exposed to DON. The pretreatment of cells with silymarin decreased the loss of cell viability induced by OTA, FB1 and DON; inhibited the formation of reactive oxygen species produced by FB1 and DON and decreased apoptosis in cells exposed to FB1 and DON. In the evaluation of the protective effects of curcumin and silymarin on liver and kidney toxicity caused by OTA and FB1 in mice, it was observed that both compounds, administered alone or in combination, were able to mitigate the harmful effects caused by mycotoxins, promoting improvement in liver and kidney function and preventing oxidative stress, in addition to preventing kidney tubular damage and hepatocyte necrosis caused by exposure to the mycotoxins OTA and FB1. In general, the results of this study demonstrated that both curcumin and silymarin provided protection against the harmful effects caused by exposure to mycotoxins. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-10-08 |
dc.date.accessioned.fl_str_mv |
2022-04-04T18:15:11Z |
dc.date.available.fl_str_mv |
2022-04-04T18:15:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/24024 |
url |
http://repositorio.ufsm.br/handle/1/24024 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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bitstream.checksum.fl_str_mv |
8ccf75fa835994967b31eaec5d3b557c 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1801485245092986880 |